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Potential metabolomic biomarkers for evaluation of adriamycin efficacy using a urinary 1H-NMR spectroscopy

Authors :
Kyu-Bong, Kim
Ji-Young, Yang
Seung Jun, Kwack
Hyung Sik, Kim
Do Hyun, Ryu
Yeon-Joo, Kim
Jung Yun, Bae
Duck Soo, Lim
Seul Min, Choi
Mi Jung, Kwon
Du Yeon, Bang
Seong Kwang, Lim
Young Woo, Kim
Geum-Sook, Hwang
Byung-Mu, Lee
Source :
Journal of applied toxicology : JAT. 33(11)
Publication Year :
2012

Abstract

A metabolomics approach using proton nuclear magnetic resonance (NMR) was applied to investigate metabolic alterations following adriamycin (ADR) treatment for gastric adenocarcinoma. After BALB/c-nu/nu mice were implanted with human gastric adenocarcinoma, ADR (1 or 3 mg kg(-1) per day) was intraperitoneally administered for 5 days. Urine was collected on days 2 and 5 and analyzed by NMR. The levels of trimethylamine oxide (TMAO, ×0.3), hippurate (×0.3) and taurine (×0.6) decreased significantly (P 0.05), whereas the levels of 3-indoxylsulfate (×12.6), trigonelline (×1.5), citrate (×2.5), trimethylamine (TMA, ×2.0) and 2-oxoglutarate (×2.3) increased significantly (P 0.05) in the tumor model. After ADR treatment, TMAO, hippuarte and taurine were increased significantly on day 5 compared with those of the tumor model. The levels of 2-oxoglutarate, 3-indoxylsulfate, trigonelline, TMA and citrate, which increased in the tumor model, significantly decreased to those of normal control by ADR treatment. Furthermore, the ratio between TMA and TMAO was dramatically altered in both tumor and ADR-treated groups. Overall, metabolites such as TMAO, TMA, 3-indoxylsulfate, hippurate, trigonelline, citrate and 2-oxoglutarate related to the tricarboxylic acid (TCA) cycle might be considered as therapeutic targets to potentiate the efficacy of ADR. Thus, these results suggest that the metabolomics analysis of tumor response to ADR treatment may be applicable for demonstrating the efficacy of anticancer agent, ADR and treatment adaptation.

Details

ISSN :
10991263
Volume :
33
Issue :
11
Database :
OpenAIRE
Journal :
Journal of applied toxicology : JAT
Accession number :
edsair.pmid..........dd7f09a4e6027ecc726809a628b74e8b